In a continuing investigation of fetal muscle, we are studying the metabolism of the cyclic nucleotides. Cyclic AMP and cGMP are higher in fetal than in adult muscle. PGE2 (2.8 micron M) stimulates cAMP accumulation in the fetal muscle (heart, diaphragm and skeletal muscle). The increase in cAMP is greater in the fetal than in the adult series. Currently we are measuring guanyl cyclase in fetal and adult rhesus muscle. Cyclic AMP phophodiesterase (PDE) activity of rhesus skeletal muscle is highest in the 100-day fetus, decreases near term and is lowest in the adult. Kinetic data indicates the existence of 2 cAMP-PDEs and 1 cGMP-PDE activities in both fetal and adult muscle. The apparent Km values for the high-affinity PDE enzyme are similar in fetal and adult muscle, whereas those for the low-affinity enzyme were 2-fold higher in the fetal series. The Vmax enzyme was 10-fold greater in fetal than in adult muscle and the low Km Vmax was 4-fold greater in the fetal muscle. The Vmax values for cGMP-PDE are also higher in fetal than in adult muscle. We are also studying metabolic control mechanisms in cardiac and skeletal muscle from the rhesus fetus. We have determined the tissue levels of the metabolic intermediates and co-factors of the glycolytic pathway and calculated the mass-action ratio for each reaction. At midterm, the apparent equilibrium constants in both types of fetal muscle are over 800 times larger than the mass-action ratios for hexokinase, phosphofructonkinase (PFK) and pyruvate kinase, evidence that these three enzymes can be regulatory early in development. Additional evidence indicates that fetal PFK is rate-limiting by midterm. In skeletal muscle the activity of PFK is 3-5 times greater in fetal (midterm) than in adult muscle, in cardiac muscle the fetal PFK activity is lower. BIBLIOGRAPHIC REFERENCES: Bocek, R.M., Young, M.K. and Beatty, C.H. Cyclic AMP in developing muscle of the rhesus monkey: Effect of prostaglandin E2. Biol. Neonate 28: 92-103, 1976. Beatty, C.H., Bocek, R.M. and Young, M.K. Rate-limiting reactions in fetal cardiac muscle. Fed. Proc. 35:365, 1976.